Date: 2015-06-09
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in the Journal of Clinical Psychiatry
Company: Alkermes (Ireland)
Product: Aristada® (aripiprazole lauroxil - ALKS 9070)
Action
mechanism: LinkeRx is a novel, proprietary technology platform developed by Alkermes that enables the creation of injectable extended-release atypical antipsychotics and other central nervous system therapies. Aripiprazole lauroxil utilizes the LinkeRx technology. Once in the body, aripiprazole lauroxil converts to aripiprazole, which is commercially available under the name Abilify®. Aripiprazole lauroxil was formerly referred to as ALKS 9070. Aripiprazole lauroxil is an investigational, novel, long-acting injectable atypical antipsychotic for the treatment of schizophrenia designed to offer patients an alternative to oral antipsychotic medicines that must be taken daily. Aripiprazole lauroxil was developed based on Alkermes' proprietary LinkeRx® technology and is designed to provide dosing flexibility to address the unique needs of patients with schizophrenia. Once in the body, aripiprazole lauroxil converts to aripiprazole (Abilify®). Aristada® was approved by the FDA in October 2015.
Disease: schizophrenia
Therapeutic area: CNS diseases - Mental diseases
Country: Bulgaria, Republic of Korea, Malaysia, Philippines, Romania, Russian Federation, Ukraine, USA
Trial
details: The phase 3, randomized, multicenter, double-blind, placebo-controlled study was designed to assess the efficacy, safety and tolerability of aripiprazole lauroxil in patients experiencing acute exacerbation of schizophrenia. The trial included adult patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®) criteria for schizophrenia and had a PANSS total score of 70 or higher at study baseline. A total of 623 patients were randomized to receive once-monthly intramuscular injections of aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg or a matching placebo injection of either low volume or high volume for 12 weeks. Following randomization, patients received their first injection along with daily oral study drug for the first three weeks. Patients randomized to the two aripiprazole lauroxil treatment groups received oral aripiprazole for those initial three weeks, while patients randomized to the placebo group received matching oral placebo for three weeks. A total of 596 patients were included in the full analysis set, as defined by those who received at least one dose of study drug and had at least one primary efficacy assessment following administration of study drug.
The primary efficacy endpoint of the study was the mean change from baseline at Week 12 in PANSS total score, using an analysis of covariance (ANCOVA) with a last observation carried forward (LOCF) approach. The Hommel procedure was used for multiple hypothesis testing. Efficacy was also analyzed using a mixed model for repeated measures (MMRM) as a sensitivity analysis.
All participants in the double-blind portion of the study were eligible to continue in an open-label phase and receive aripiprazole lauroxil for an additional 12 months. The objective of the extension phase of the study is to assess the safety and long-term durability of effect of once-monthly aripiprazole lauroxil. (NCT01469039)
Latest
news: * On February 25, 2016, Alkermes announced positive topline data from a randomized, open-label, pharmacokinetic study evaluating a two-month dosing interval of Aristada® (aripiprazole lauroxil) extended-release injectable suspension for the treatment of schizophrenia. Results from the study showed that the 1064 mg dose of Aristada® achieved therapeutically relevant plasma concentrations of aripiprazole with a PK profile that supports dosing once every two months. The most common adverse events for the two-month dosing interval were injection site pain and dyskinesia. Based on these results, Alkermes plans to submit a supplemental New Drug Application (sNDA) to the FDA in the second half of 2016. Results of the study served as the basis for Alkermes' New Drug Application (NDA) to the FDA to gain marketing approval of aripiprazole lauroxil for the treatment of schizophrenia, with a regulatory action date of Aug. 22, 2015. * On June 18, 2014, Alkermes announced the presentation of data from its phase 3 clinical trial of aripiprazole lauroxil, an investigational drug candidate in development for schizophrenia, at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting in Hollywood, Fla. In the pivotal study, both doses of aripiprazole lauroxil tested, 441 mg and 882 mg administered once-monthly, met the primary endpoint with statistically and clinically significant reductions in Positive and Negative Syndrome Scale (PANSS) scores, met all secondary endpoints and demonstrated significant improvements in schizophrenia symptoms versus placebo. This is the first demonstration of the efficacy of a range of doses of a long-acting injectable form of aripiprazole in a randomized clinical trial. The company remains on track to submit a New Drug Application (NDA) to the FDA in the third quarter of 2014. During the 12-week, double-blind treatment period, patients treated once-monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically and clinically significant placebo-adjusted mean reductions from baseline in PANSS total scores (-10.9 points, p Overall, 64% of patients who received aripiprazole lauroxil completed the study, compared to 46% of patients who received placebo. Aripiprazole lauroxil was generally well tolerated in the study, and the observed safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache. * On April 8, 2014, Alkermes has announced positive topline results from a randomized, double-blind, placebo-controlled phase 3 clinical trial of aripiprazole lauroxil in patients with schizophrenia. Patients treated once monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) total scores at week 12, compared to placebo (pAripiprazole lauroxil was generally well tolerated in the phase 3 study, and the safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache. Alkermes will present comprehensive data from the phase 3 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal. * On October 8, 2013, Alkermes has announced completion of patient enrollment in the pivotal, multinational phase 3 study evaluating aripiprazole lauroxil in patients with schizophrenia. Aripiprazole lauroxil is designed to provide patients with once-monthly dosing of a medication that, once in the body, converts into aripiprazole, a molecule that is commercially available under the name Abilify®. Alkermes continues to expect topline results from the phase 3 study in the first half of 2014. The clinical data from this study will form the basis of a New Drug Application (NDA) to the FDA for aripiprazole lauroxil for the treatment of schizophrenia. Enrollment was completed following a prespecified interim analysis of sample size. This analysis, designed to preserve the integrity of the final efficacy analysis and performed by an independent statistical center, indicated that a sample size of 540 patients or more would have sufficient statistical power to evaluate the primary endpoint. The study continues to be blinded until completion.
* On June 9, 2015, Alkermes announced the publication of results from its phase 3 clinical trial of aripiprazole lauroxil for the treatment of schizophrenia in the Journal of Clinical Psychiatry. Data from the trial showed that multiple dose strengths of aripiprazole lauroxil administered once monthly demonstrated statistically significant reductions in schizophrenia symptoms, compared to placebo. The phase 3, randomized, multicenter, double-blind, placebo-controlled study of aripiprazole lauroxil evaluated 623 patients with schizophrenia. Patients treated once monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) total scores at Week 12, compared to placebo. The improvement from baseline to Week 12 in PANSS total scores was clinically meaningful and statistically significant in both aripiprazole lauroxil dose groups, with a placebo-adjusted mean PANSS score reduction of 10.9 points for the 441 mg dose group (p<0.001) and 11.9 points for the 882 mg dose group (p<0.001). In addition to meeting the prespecified primary efficacy endpoint of PANSS total score reduction, the study also met the prespecified key secondary endpoint of improvement on the Clinical Global Impression - Improvement (CGI-I) scale for each aripiprazole lauroxil group versus placebo at Week 12 (p<0.001). Both of the aripiprazole lauroxil dosing groups demonstrated significant improvement at all post-baseline visits. Furthermore, all other secondary endpoints were found to be statistically significant across both doses. Aripiprazole lauroxil was generally well tolerated in the phase 3 study. The most common adverse events in the study were insomnia, akathisia and headache.
